Feasibility of cardiovascular population-based CT screening
Vonder, Marleen
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3
Coronary artery calcium imaging
in the ROBINSCA trial: Rationale,
design and technical background
Marleen Vonder
Carlijn M. van der Aalst
Rozemarijn Vliegenthart
Peter M.A. van Ooijen
Dirkjan Kuijpers
Jan Willem Gratama
Harry J. de Koning
Matthijs Oudkerk
Published in Academic Radiology
2018, Vol. 25, no. 1, pp 118-128
Abstract
Rationale and Objectives
To describe the rationale, design, and technical background of coronary artery calcium
(CAC) imaging in the large-scale population-based cardiovascular disease screening
trial (ROBINSCA).
Methods
First, literature search was performed to review the logistics, set-up and settings of
previous performed CAC imaging studies, and current clinical CAC imaging protocols
of participating centers in the ROBINSCA trial were evaluated. A second literature
search was performed to evaluate the impact of computed tomography parameter
settings on CAC score.
Results
Based on literature reviews and experts opinion an imaging protocol accompanied by
data management protocol was created for ROBINSCA. The imaging protocol should
consists of a fixed tube voltage, individually tailored tube current setting, mid-diastolic
electrocardiography-triggering, fixed field-of-view, fixed reconstruction kernel, fixed
slice thickness, overlapping reconstruction and without iterative reconstruction. The
analysis of scans is performed with one type and version of CAC scoring software, by
2 dedicated and experienced researchers. The data management protocol describes the
organization of data handling between the coordinating center, participating centers
and core analysis center.
Conclusion
In this paper we describe the rationale and technical considerations to be taken in
developing CAC imaging protocol and we present a detailed protocol that can be
implemented for CAC screening purposes.
3
Introduction
Early detection of cardiovascular disease (CVD) followed by evidence-based treatment,
could potentially reduce CVD morbidity and mortality [1,2]. Extent of coronary artery
calcium (CAC) is a strong risk marker for coronary events, with evidence mainly
derived from observational studies and from prospective non-randomized studies
[3,4]. So far, there is no evidence that CAC imaging followed by treatment leads to
a decrease in CVD morbidity and mortality as prospective randomized studies on
CVD risk stratification based on CAC imaging combined with treatment are lacking.
Consequently, European and North-American guidelines on CVD prevention
still classify the evidence for CAC imaging at level IIb (‘may be considered’) in
asymptomatic adults at intermediate risk [1,2] and mention that CAC imaging should
not be uncritically used as a screening method [5,6]. However, there is an ongoing
debate on whether and how a randomized controlled trial (RCT) to determine the
risk or benefit of screening for CVD by CAC imaging should be performed [7]. Issues
related to RCT in CVD screening by CAC imaging, regarding radiation safety, imaging
protocols, and privacy, and ethical and economic considerations, have been addressed
by many experts in the field of CAC imaging [7–9]. A well-described study design is
essential when performing an RCT in CVD screening by CAC imaging. Moreover,
in the case of such a trial, CAC imaging will most likely be performed in multiple
centers involving many operators, technicians and analysts. To use the CAC score
as a quantitative imaging biomarker in a trial, the CAC score needs to be accurate,
consistent, reliable, and valid across CT platforms, clinical sites and over time [10],
demanding development of a robust and well-fitted imaging protocol.
In this paper we describe the rationale, design, and technical background of CAC
imaging within the framework of the Dutch large-scale population-based cardiovascular
screening trial, ROBINSCA (Risk Or Benefit In Screening for Cardiovascular Disease).
The ROBINSCA trial
Currently, the identification of asymptomatic persons at risk of CVD is often based
on well-known risk factors, including age, gender, smoking, diabetes, and levels of
cholesterol and blood pressure. In Europe, the most commonly employed risk model
is the Systematic Coronary Risk Evaluation (SCORE) chart, estimating a person’s risk
of developing fatal CVD within a 4-year period [6].
In 2014, the Dutch population-based screening trial “ROBINSCA: Risk OR Benefit
IN Screening for CArdiovascular disease” started. The primary objective of the trial
3
is to establish whether CAC imaging in asymptomatic men and women (screenees)
followed by preventive treatment will reduce coronary heart disease (CHD)-related
mortality and morbidity by at least 15% compared with traditional risk factor
assessment (SCORE) after 5 years of follow-up. Moreover, the trial will also show
whether screening by the SCORE method followed by treatment is favorable in
reducing CVD compared to no screening. Although CVD screening by the SCORE
method is a class 1 recommendation, so far, no RCTs have been performed showing
the added value of treatment following SCORE screening (level of evidence: C) [6].
In the ROBINSCA trial, approximately 39,000 participants will be included and
randomized (1:1:1) into three groups: intervention group A (screening for CVD
risk by means of SCORE), intervention group B (screening for CVD risk by means
of CT scanning to determine the CAC score), or control group (no screening), see
Figure 1. Currently, three Dutch regions (Apeldoorn, The Hague, and Groningen) are
participating in this trial. CT screening is performed at Gelre Hospital (Apeldoorn),
Bronovo Hospital (The Hague) and University Medical Center Groningen (Groningen).
The ROBINSCA trial has received authorization of the Minister of Health, Welfare and
Sports, after a positive advice of the Health Council of the Netherlands in August 2013
and received an Advanced Grant from the European Research Council.
Materials and methods
To develop a well-fitting imaging protocol for the ROBINSCA trial, we performed
literature searches to review (1) the logistics, setup, and settings of previous CAC
imaging studies and (2) the impact of CT parameter settings on CAC score. In the first
literature search, we searched for patient studies on CAC scoring. Literature search
was performed in PubMed and Web of Science, and restricted to studies published
from 2000 until 2016, to get a comprehensive and up-to-date overview of recent CAC
scoring studies. The following search terms were used: coronary calcium scoring;
calcification; coronary artery; atherosclerosis; cardiovascular disease; coronary
disease; computed tomography; scan. Only CAC studies containing 200+ individuals
were included, and coronary CT angiography and phantom studies were excluded.
For the second literature search to determine the impact of CT parameter settings,
the following additional terms were used: tube voltage; tube current; heart rate; body
size; chest size; iterative reconstruction; kernel; computer applications; software. CAC
studies containing individuals or phantoms were included and Computed Tomography
Angiography studies were excluded. Included literature was reviewed per impact
parameter. Furthermore, we evaluated the CAC imaging protocols that are currently
used in the participating imaging centers.
In the ROBINSCA trial, a second-generation dual-source computed tomography
(DSCT) system (Somatom Flash, Siemens, Erlangen, Germany) is used in all
participating centers. Parameter settings that can impact the CAC score, as could be
established from the literature search, were evaluated for second-generation DSCT,
and specific questions regarding CT parameter settings were analyzed by performing
phantom and patient measurements. Experts in the field of radiology, cardiology, and
clinical physics not necessarily involved in the ROBINSCA trial were asked for their
opinion and expertise to optimize and fine-tune the final imaging protocol. The final
protocol was tested and examined for inter- and intra- scanner reproducibility and
image quality for all involved CT systems. The final result was a CAC imaging protocol
for second-generation DSCT accompanied by a data management protocol.
Results
Imaging protocols in previous CAC studies
In the last decades, many large CAC imaging studies have been performed. Many used
electron beam computed tomography (EBCT). Agatston et al. (1990) first designed
a scoring system of the amount of coronary calcification on EBCT scans, afterwards
called the Agatston or CAC score [11]. Later on, studies also used multi-detector
computed tomography and dual-source computed tomography (DSCT) for CAC
imaging. Details of the imaging protocols of these studies are presented in Table 1. For
EBCT studies, settings were usually similar for acquisition (e.g. tube voltage and tube
current) and reconstruction parameters (slice thickness and increment etc.) [12–28].
Only settings for field-of-view (FOV) and slice thickness differed [12–28]. Corrections
were applied for slice thickness or voxel size to account for these differences prior to
calculation of the CAC score. However, in many MDCT or DSCT studies, information
about parameter settings is often poorly documented. Many CAC imaging studies only
give a short description of the imaging protocol, or only refer to the imaging protocol
as: ‘standard non-contrast scan was performed’ and ‘manufacturer’s recommended
protocol was used’ [29,30]. The few studies that have published the imaging protocol
reveal differences in parameter settings, which could affect the CAC score and impact
CVD risk stratification.
A small survey among the participating centers in the ROBINSCA trial showed that
there are also quite a few differences in current, clinically used CAC imaging protocols
for same generation CT systems of the same vendor. Differences were present in any
3
step of the protocol: acquisition (i.e. high-pitch spiral and sequential scan mode, tube
current settings), reconstruction (i.e. FOV size) and analysis.
Impact of parameter settings on CAC score
Screenee characteristics together with the type of CT scanner and specific CT imaging
parameters can impact the CAC score. Important screenee characteristics are the
person’s chest size (habitus, gender, body mass index), (ir)regularity of the heart rate
and heart rate frequency. Additionally, various types of CT systems can be used for
CAC imaging with different hardware and software parameter configurations.
Screenee characteristics: Increased (chest) body size, defined by a person’s body mass
index, leads to lower attenuation values of CAC [31–33]. Even though an increased
tube current is used for large or obese body sizes to compensate for increased noise
levels, the CAC score is underestimated compared to normal or under-weight body
sizes [34]. This is due to the increased beam-hardening effect in larger body size,
impacting the energy-spectrum of an x-ray beam, which cannot be counteracted by
a higher tube current. Also female anatomy (breast size) and coronary vessel size can
impact CAC scoring [35].
Heart rate and vessel displacement: Increasing heart rate and vessel displacement
leads to blurred spots where the calcifications are present on a CT-image; this also
generally decreases the CAC score [36–39]. More specifically, Groen et al. showed that
calcifications with a relatively low density lead to decreased scores, whereas very high
density calcifications increase the CAC score [37].
Electrocardiography (ECG) triggering: To reduce the influence of cardiac motion, fast,
ECG-triggered scanning is used in CAC imaging. The optimum cardiac phase with
least motion and scan variability is at mid-diastole at 60-75% of the R-R interval, for
heart rates below 70 bpm. For heart rates >70 bpm, end-systolic ECG-triggering at
40-45% of R-R interval is recommended [40,41]. Nevertheless, mid-diastolic
ECG-triggered scanning in high heart rates also showed favorable results, paving the way for
mid-diastolic ECG triggering in all individuals, regardless of heart rate [41].
Tube voltage: Tube voltage reduction from 120 kVp to 80-100 kVp leads to reduced
radiation dose, more accurate depiction of low density calcifications, but overall leads
to overestimation of the CAC scores when a default CAC threshold of 130 Hounsfield
units (HU) is used [42–45]. The CAC threshold can be adapted for better agreement
to the original 120 kVp imaging protocol [46,47]. However, the CAC score according
to Agatston is a multi-threshold measurement, and therefore scans acquired at lower
tube voltage settings could still show significantly higher CAC scores compared to the
original 120 kVp imaging protocol for individuals [42]. Therefore, other tube voltage
settings than 120 kVp should be avoided in CAC imaging.
Tube current: Another way for reducing the radiation dose in CAC imaging is to reduce
the tube current. Although CAC scores are generally not affected by lowering the tube
current, the noise level of CAC images should remain below a certain threshold (<20
HU) [48,49], to allow accurate quantification of for instance very small calcifications
in obese individuals [49]. Nowadays, attenuation-based tube current adaptation can
be applied, resulting in efficient dose usage for small to very large body sizes [50,51].
Slice thickness and increment: Reconstruction of thinner slices (i.e. smaller than
the regular 3.0 mm) results in increased reproducibility, increased CAC scores and
increased sensitivity to detect small calcifications, probably due to reduced partial
volume effect because of smaller voxel size [37,52–58]. However, to maintain the same
image noise level for thin slice reconstruction, the tube current needs to be increased,
leading to higher radiation dose. Alternatively, in 3.0 mm reconstruction, the slice
increment between adjacent slices can be decreased to create overlapping slices, also
resulting in increased reproducibility, without the necessity to increase tube current
[56,59–61].
Kernel/FOV: Sharper reconstruction kernels increase the CAC score, and FOV can
impact the number of detected calcifications [62,63].
Iterative reconstruction: Iterative reconstruction algorithms can compensate for the
higher image noise in low tube current or thin slices. Various iterative reconstruction
algorithms from the CT vendors have been examined, allowing radiation dose
reductions up to 82% [64–75]. Although in most studies the CAC scores showed
good agreement with the default filtered-back-projected reconstructions, CAC scores
were significantly lower [35,64–70,72,74–76]. This could lead to reclassification of
individuals into a lower risk category, and thus, to underestimation of the CVD risk
[68,76].
Scoring Software: Lastly, analysis parameters defined by the user or set by the software
package can impact the CAC score. For instance, definition of a calcification by way
of pixel connectivity, number of adjacent voxels, manual or automatic selection of
calcifications all impact the CAC score [77,78]. Also, different CAC software packages
for identical CT data sets can yield absolute differences in CAC scores [77].
3
Ta bl e 1 – C or on ar y a rt er y c alci um im ag in g s tudies a nd t heir p ro to co l s et tin gs Stu dy Au tho r Ye ar N Sc anne r ty pe EC G trig ge -rin g (R -R in te rva l) Sc an mo de Tu be vol ta ge Tu be curr en t Re con A na ly sis St . F ra ncis H ea rt S tu dy A rad et al . [12] 2000 1238 EB CT (Im at ro n C-150XP) 80% 100 m s p er slice -3.0 mm (co nt i-guo us), FO V 35 cm Thr es ho ld: 130 HU ≥2 ad jacen t p ix els (≥0.93mm 2) A rad et al . [13] 2001 5582 EB CT (Im at ro n C-150XP) 80% 100 m s p er slice -3.0 mm (co nt i-guo us), FO V 26 cm, pix el a re a 0.51 mm 2 Thr es ho ld: 130 HU ≥2 ad jacen t p ix els CARD IA stu dy Ir ib ar ren et a l. [14] 2000 374 EB CT EC G ga te d Sc an tim e: 100 m s -3.0 mm ≥6 ad jacen t p ix els (≥2mm 2) Ca rr et. al . [15] 2005 3044 Se e MESA Pro an d re -tro sp ec tiv e 80% Ya n et a l. [16] 2006 2913 EB CT , MD CT -2 s eq uen tia l sc an s -2.5-3.0 mm ≥6 ad jacen t p ix els (≥2mm 2) So uth B ay H ea rt Wa tc h Pa rk et a l. [17] 2002 1461 EB CT (Im at ro n C-100) 80% -6.0 mm Se e MESA (≥4.1 mm 3) Q u et a l. [18] 2003 1312 EB CT (Im at ro n C-100) 80% 100 m s exp os ur e -6.0 mm Se e MESA 3.0 mm (n=319 va lid at i-on p ur pos es) G re en -la nd et a l. [19] 2004 1461 (EB)CT -6.0 mm Se e MESAStu dy Au tho r Ye ar N Sc anne r ty pe EC G trig ge -rin g (R -R in te rva l) Sc an mo de Tu be vol ta ge Tu be curr en t Re con A na ly sis -Sh aw et al . [20] 2003 10377 EB CT (I m a-tro n C-100, Im at ro n C-150) 60-80% 100 m s -3.0 mm s lice thic kn es s Thr es ho ld: 130 HU Ra gg i et al . [21] 2004 co nt iguo us ≥3 co nt iguo us pix els (1.03 mm 3) -Ko ndos et a l. [22] 2003 8855 EB CT (Im at ro n C-100) 80% 100 m s -3.0 mm, FOV 260 mm, 512 m at rix, sh ar p k er nel Thr es ho ld: 130 HU ≥4 ad jacen t p ix els (1.0 mm 2) C oo pe r Cl i-ni c D al las Ch en g et al . [23] 2003 17967 EB CT (S iem en s Ev olut ion C-150XP) -100 m s -3.0 mm s lice thic kn es s -2.0 mm in cr e-m ent LaM on te et a l. [24] 2005 10746 EB CT -Ch ur ch et a l. [25] 2007 10746 EB CT (I m a-tro n C-150 XP , I m at ro n C-300) -3.0 mm s lice thic kn es s -2.0 mm in cr e-m ent MESA Ca rr et. al . [15] 2005 6814 EB CT Pr os pe ct iv e, 80% Se quen tia l mo de 130 kV p 63 mA s 3.0 mm, FO V 350 mm ≥5.5 mm 3 MD CT : 4 det ec t r ow Seq ue nti al Ta bl e 1 Co nt in ue d
3
Stu dy Au tho r Ye ar N Sc anne r ty pe EC G trig ge -rin g (R -R in te rva l) Sc an mo de Tu be vol ta ge Tu be curr en t Re con A na ly sis MD CT Pr os pe ct iv e, 50% Se quen tia l 140 kV p 50 mA s 2.5 mm, FOV 350 mm ≥4.6 mm 3 Pr os pe ct iv e, 50% Se quen tia l 120 kV p 106 mAs Ret ros pe ct iv e, 50% 120 kV p 320 mAs Ro tte rd am C or on ar y Ca lcifi ca ti-on S tu dy V lieg en t-ha rt et a l. [26] 2005 1795 EB CT (Im at ro n C-150) 80% 100 m s p er slice -3.0 mm Thr es ho ld: 130 HU ≥2 ad jacen t p ix els (0.65mm 2) PA CC pr oj ec t Ta ylo r et al . [27] 2005 2000 EB CT (Im at ro n C-150 LXP) 60-80% -3.0 mm s lice thic kn es s Thr es ho ld: 130 HU ≥4 co nt iguo us pi xe ls Fr amin g-ha m H ea rt Stu dy M os ele w -sk i et a l. [80] 2005 612 8-s lice D CT (L ig hts pe ed U ltra GE) 50% Seq ue nti al 120 kV p 320 mA 2.5 mm s lice thic kn es s Thr es ho ld: 130 HU 400 mA co nt iguo us ≥3 co nn ec te d pi xe ls HNR , ECA C Sc hm er -m un d et al . [28] 2007 ongo ing EB CT (Im at ro n C-100, C-150) 80% 100 m s 3.0 mm s lice thic kn es s Thr es ho ld: 130 HU C on tiguo us ≥4 co nt iguo us pi xe ls CO NFIRM reg istr y M in et a l. [81] 2011 27125 MD CT , DSCT -SC O T-HEAR T N ew by et al . [82] 2012 ~2070 64, 128, 320 MD CT -Thr es ho ld: 130 HUStu dy Au tho r Ye ar N Sc anne r ty pe EC G trig ge -rin g (R -R in te rva l) Sc an mo de Tu be vol ta ge Tu be curr en t Re con A na ly sis Jac ks on H ea rt S tu dy Li u et a l. [83] 2012 2880 MD CT (L ig hts pe ed 16 P ro , GE) -NHLB I F a-mi ly H ea rt stu dy Robb in s et a l. [84] 2014 1848 MD CT 50% Se quen tia l, 0.5 s ga nt ry ro ta tio n, tem p. r es. 250-300 m s. 120 kV 160 mAs 2.5 mm, FOV 350 mm Thr es ho ld: 130 HU ≥2 co nn ec te d pix els (0.9 mm) RO MI CA T II tri al Pur sn ani et a l. [29] 2015 473 MD CT , DSCT -(GE 64-S lice L ig hts pe ed , GE L ig hts pe ed V CT , S iem en s 64-S lice S en sa tio n, S iem en s D ua l S our ce 64-S lice D efini tio n, S iem en s D ua l S our ce 128-S lice Fl as h, a nd P hi lips Br illi an ce 256-S lice iCT) EU -RO-C CAD N ico ll et al . [85] 2016 5515 MD CT -4-256 s lices -3.0 mm ≥4 co nt iguo us pi xe ls CRESCENT Lu bb er s et a l. [86] 2016 242 CT -Ta bl e 1 Co nt in ue d
3
Design CAC imaging protocol
Preparation: A calcium mass calibration mat (QCT-bone mineralTM phantom, Image
analysis, Columbia, USA) is placed on the CT table. A participant is positioned in a
supine position, feet-first with the arms positioned above the head. ECG-electrodes
are placed according to default instructions.
Acquisition: A topogram is acquired in craniocaudal direction, starting at the top
of the lungs down to the diaphragm. Next, the craniocaudal window for the CT
Table 2 – CT acquisition protocol for CAC scoring scanScan parameters CT protocol
A B
Scan mode High-pitch spiral Sequential
Pitch 3.4
-Tube voltage (kVp) 120
Tube current (ref. mAs) 80
Rotation time (ms) 280
Collimation (mm) 128×0.6
Matrix 512×512
ECG triggering Prospective, 60%
Dose modulation CareDose 4D, semi, enter ref mAs
API Inspiratory breath-hold
Direction Craniocaudal
Upper limit Below carina
Lower limit Apex/bottom edge heart
Table 3 – CT reconstruction protocol for CAC scoring scan A and B
Reconstruction 1 Reconstruction 2 Reconstruction 3
Slice thickness (mm) 3.0 1.5 3.0
Slice increment (mm) 1.5 1.0 1.5
FOV (mm) 250 250 Maximum
Kernel b35f (sharp)
Algorithm Filtered-back projection
Window Mediastinum
Window width (HU) 350
scan is set, with upper limit at one centimeter below the carina and lower limit at
approximately two centimeters below the apex of the heart. The axial window setting
is not customized, since this would change the FOV affecting reconstruction results. A
default tube voltage of 120 kVp is used and tube current (dose) modulation is set at a
quality reference of 80 mAs. Prospective ECG triggering is used; images are acquired
at 60% of the R-R interval, during inspiratory breath-hold. In-build cardiac software
‘Flash check’ allows to check the regularity of the heart rate, necessary for confirming
a certain time-window to scan the whole heart within one heartbeat. The ‘Flash check’
is performed before starting the actual acquisition. A high-pitch spiral scan protocol
with a pitch of 3.4, is applied in participants with a regular heart rate of <65 beats per
minute (bpm). In participants with an irregular heart rate or heart rate of ≥65 bpm,
a sequential CAC scan is acquired. The acquisition parameters are shown in Table 2.
Reconstruction: The acquired CAC scan is reconstructed three times, with slightly
different reconstruction parameter settings. By default, the images are reconstructed
with a slice thickness of 3.0 mm and slice increment of 1.5 mm. Images are reconstructed
with filtered-back projection and a FOV of 250 mm with a sharp reconstruction kernel
(b35f). Images are transferred with a default mediastinal window setting. Table 3
shows the image reconstruction parameters.
Analysis: One complete image data set consists of: 1) Patient protocol, including an
overview of scan parameters; 2) Topogram, scout image of the thorax; 3) ECG image,
Figure 2 – Imaging data management ROBINSCA trial. (1) The coordinating center schedules the partici-pants per participating center. (2) A CAC scan is made and all imaging data are transferred to the analyzing center. Image data is analyzed and (3) outcomes are transferred to the coordinating center, (4) which com-municates this outcome including advice to the GP and participant (and if necessary, a medical specialist is consulted.) (5) Requests for CAC scans can be done at the coordinating center, (6) which anonymizes the request for the analyzing center. Next, (7) the CAC scan is transferred to the requesting specialist.3
acquired during CAC scan; 4) CT scan for CAC scoring, available as three reconstructed
image stacks. Image data sets are analyzed for: (1) Completeness (e.g. right acquisition
protocol applied? all reconstructions present?); (2) Radiation dose, (3) Image quality
(e.g. any image artifacts?); (4) Quantitative measurements (e.g. thorax diameter, CAC
scores); (5) Incidental findings. Images are analyzed using dedicated CAC scoring
software (CaSc, Syngo.via, Siemens, Erlangen Germany). Semi-automatic selection of
calcifications is performed per coronary artery. A calcification is defined as a region
with a peak value of ≥130 HU and comprising ≥2 adjacent voxels (eight-connected
connectivity) [11,78]. Standard scoring algorithms for Agatston score, volume score
and mass score are used and results are archived [79].
Design imaging data management
Participants are scheduled for a CAC scan in one of the three participating centers by
the coordinating center, see Figure 2. Each participant has a unique study identification
number that is used throughout the study process, according to ICH-GCP guidelines.
Participant identification is checked at the local participating center and CAC imaging
Table 4 – Incidental findings on CT scan for CAC scoring that are (not) reported to GP and participantReported Not reported
Chest Aortic aneurysm ≥50 mm Valve calcification (aortic valve, mitral valve, etc) Pulmonary mass (e.g. calcified pleural
plaques, nodules) Pericardial abnormalities (thickening, calcifica-tion, etc)
Pleural fluid, ≥2 cm thickness Annulus calcification
Hiatus hernia
Abdomen Very large liver cyst(s) Small to medium size liver cyst(s) Identifiable abdominal mass
Ascites
Table 5 – Cardiovascular risk stratification based on the CAC score
Calcium score Extent of atherosclerotic coronary artery disease Cardiovascular disease risk
0 No identifiable plaque Low
1-10 Mild identifiable plaque Low
11-99 Definite, at least mild atherosclerotic plaque Low 100-399 Definite, at least moderate atherosclerotic plaque High ≥ 400 Extensive atherosclerotic plaque Very high
is performed according to the described protocol by trained technicians with over 5
years of experience with ECG-triggered CT scanning. The scan is acquired within 10
minutes, and is saved under (only) study ID number. The anonymous image data sets
are transferred via a secured network connection to the analyzing center. Research
personnel (background in (technical) medicine or radiology technicians) analyze
the image data sets in a digital research workspace. Results are archived to a research
picture archiving and communication system (PACS). Per participant, a digital Case
Report Form (eCRF) is created. The eCRF contains CAC scores, radiation dose
parameters and comments if applicable.
A clinically relevant incidental finding can potentially be detected on the CAC scan,
that may require further management if not previously known. All incidental findings
are logged by radiologists (see Table 4), but only potentially clinically relevant findings
are reported in the eCRF. The eCRF is transferred by the analyzing center to the
coordinating center. The coordinating center has the key for participant identification
based on study ID, to process the results. The coordinating center communicates the
CVD risk categorization based on the CAC score (see Table 5), subsequent treatment
advice, and possible incidental findings to the participant’s general practitioners (GP)
and to the participant. A participant will not be informed on incidental findings when
indicating in the informed consent that feedback on incidental findings is not wanted.
However, the GP will always be informed about these findings. If deemed necessary
by the GP, a participant can be referred to a medical specialist (e.g. cardiologist,
pulmonologist) for further evaluation based on (very high) CAC score or incidental
findings. Participants with a high or very high CVD risk (see Table 5) will be treated
by their GP accordingly to Dutch CVRM guidelines as ‘patients with coronary heart
disease’, and statins and ACE-inhibitors are prescribed, see Figure 1.
The GP or medical specialists can request the coordinating center for the image data
of a participant. The coordinating center anonymizes the request for the analyzing
center, which returns the requested image data set. The data set is de-anonymized and
transferred to the GP or medical specialist via a secured network.
Discussion
There is a need for prospective randomized studies that can show the risk and benefit
in CVD risk stratification based on CAC scoring. In this paper we describe the
rationale and technical considerations in developing a robust and standardized CAC
imaging protocol and present a detailed protocol that can be implemented for CAC
3
imaging for screening purposes. The imaging protocol includes a fixed tube voltage,
individually tailored tube current setting, mid-diastolic ECG triggering, fixed FOV,
fixed reconstruction kernel, fixed slice thickness, overlapping reconstruction and no
iterative reconstruction. Analysis of the scans is performed with one type and version
of CAC scoring software, by dedicated researchers experienced in CAC scoring.
Altogether, the protocol results in scans with good image quality for evaluating CAC,
at a low radiation dose, from which reliable CAC scores can be derived and CVD
risk stratification can be determined. The data management protocol describes the
organization of data handling between the coordinating center, participating centers
and analyzing center.
The described imaging protocol is optimized for 2nd generation DSCT and detection
of CAC. Before this protocol can be used for other CT systems/generations, validation
is needed. Future studies have to show the impact of different generations of DSCT
with this protocol on CAC score.
To conclude, we present a detailed CAC imaging protocol and data management
protocol that are used in the ROBINSCA trial.
References
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